Our capacity to properly address the worldwide incidence of infectious diseases lies in the ability to detect, prevent, and effectively treat these infections. With increasing overuse and misuse of antibiotics, infectious bacteria have become increasingly antibiotic-resistant. Therefore, identifying and analyzing inhibitory agents is a worthwhile endeavor since few new antibacterial compounds have been produced in recent decades. The use of natural nanominerals to heal skin infections has been evident since the earliest recorded history, and specific clay minerals may prove valuable in the treatment of bacterial diseases, including infections for which there are no effective antibiotics, such as Buruli ulcer and multi- drug resistant infections. The rationale for the proposed research is based on several observations and realizations: (a) Specific clay minerals have been used to treat and heal children afflicted with Buruli ulcer, a necrotic cutaneous infection caused by Mycobacterium ulcerans;(b) Susceptibility testing of the minerals that were used to treat Buruli ulcer and two additional minerals revealed bactericidal or bacteriostatic activity against several different bacterial pathogens, including antibiotic-resistant strains;and (c) Use of antibacterial minerals would provide an inexpensive, alternative therapeutic treatment for topical infections. Considering the lack of therapeutics for treating necrotic M. ulcerans infections and other life-threatening skin infections, such as MRSA, our goals are to validate the observations that specific minerals can heal bacterial infections by investigating broad-spectrum antibacterial characteristics of the clay minerals and determining the mechanism of action of these bioactive minerals. We propose to (1) assess the broad-spectrum antibacterial effects of natural nanominerals, (2) evaluate the ability of hydrated minerals to treat topical bacterial infections in mice, and (3) determine the mechanism of action of the natural antibacterial minerals and how the minerals structurally and transcriptionally affect bacterial cells. PUBLIC HEALTH RELEVANCE: Through the use of antimicrobial susceptibility testing, we have established that certain clay minerals kill or inhibit the growth of pathogenic bacteria. In an era when few new antibiotics are being discovered, we are investigating natural nanominerals as a potential source of alternative therapeutic agents. Using microbiology, molecular biology, biochemistry, and medical/clinical approaches, we seek to determine the susceptibility patterns of bacterial pathogens to these antibacterial minerals, validate the use of specific minerals for the treatment of topical skin infections, and understand the bactericidal mechanism of action.